title: ATLAS: randomized, double-blind, placebo-controlled, phase IIIB trial comparing bevacizumab therapy with or without erlotinib, after completion of chemotherapy, with bevacizumab for first-line treatment of advanced non-small-cell lung cancer.
abstract: OBJECTIVE
  This phase III trial was performed to assess the potential benefit of adding maintenance erlotinib to bevacizumab after a first-line chemotherapy regimen with bevacizumab for advanced non-small-cell lung cancer (NSCLC).
  
  
  METHODS
  One thousand one hundred forty-five patients with histologically or cytologically confirmed NSCLC (stage IIIB with malignant pleural effusion, stage IV, or recurrent) received four cycles of chemotherapy plus bevacizumab. Seven hundred forty-three patients without disease progression or significant toxicity were then randomly assigned (1:1) to bevacizumab (15 mg/kg, day 1, 21-day cycle) plus either placebo or erlotinib (150 mg per day). The primary end point was progression-free survival (PFS).
  
  
  RESULTS
  Median PFS from time of random assignment was 3.7 months with bevacizumab/placebo and 4.8 months with bevacizumab/erlotinib (hazard ratio [HR], 0.71; 95% CI, 0.58 to 0.86; P < .001). Median overall survival (OS) times from random assignment were 13.3 and 14.4 months with bevacizumab/placebo and bevacizumab/erlotinib, respectively (HR, 0.92; 95% CI, 0.70 to 1.21; P = .5341). During the postchemotherapy phase, there were more adverse events (AEs) overall, more grade 3 and 4 AEs (mainly rash and diarrhea), more serious AEs, and more AEs leading to erlotinib/placebo discontinuation in the bevacizumab/erlotinib arm versus the bevacizumab/placebo arm. The incidence of AEs leading to bevacizumab discontinuation was similar in both treatment arms.
  
  
  CONCLUSIONS
  The addition of erlotinib to bevacizumab significantly improved PFS but not OS. Although generally well tolerated, the modest impact on survival and increased toxicity associated with the addition of erlotinib to bevacizumab maintenance mean that this two-drug maintenance regimen will not lead to a new postchemotherapy standard of care.
authors.affiliation: Bruce E. Johnson, Dana-Farber Cancer Institute, Boston, MA; Fairooz Kabbinavar, University of California Los Angeles, Translational Oncology Research International, Los Angeles; Louis Fehrenbacher, Kaiser Permanente Northern California, Vallejo; Chin-Yu Lin and Chris Bowden, Genentech, South San Francisco; Jonathan Polikoff, Southern California Permanente Medical Group, San Diego, CA; John Hainsworth, Sarah Cannon Research Institute, Nashville, TN; Saifuddin Kasubhai, Northwest Medical Specialties, Tacoma, WA; Bruce Kressel, Sibley Memorial Hospital, Washington, DC; Thomas Marsland, Integrated Community Oncology Network, Orange Park; Mark Rubin, Florida Cancer Specialists, Fort Myers, FL; Taral Patel, The Mark H. Zangmeister Center, Columbus, OH; Leonard White, Arch Medical Services, The Center for Cancer Care and Research, Saint Louis, MO; Vincent Miller, Weill Cornell Medical College and Thoracic Oncology Service, Memorial Sloan-Kettering Cancer Center, New York, NY; and James Chih-Hsin Yang, National Taiwan University, Taipei, Taiwan.
authors.forename: Bruce E
authors.initials: BE
authors.lastname: Johnson
authors.forename: Fairooz
authors.initials: F
authors.lastname: Kabbinavar
authors.forename: Louis
authors.initials: L
authors.lastname: Fehrenbacher
authors.forename: John
authors.initials: J
authors.lastname: Hainsworth
authors.forename: Saifuddin
authors.initials: S
authors.lastname: Kasubhai
authors.forename: Bruce
authors.initials: B
authors.lastname: Kressel
authors.forename: Chin-Yu
authors.initials: CY
authors.lastname: Lin
authors.forename: Thomas
authors.initials: T
authors.lastname: Marsland
authors.forename: Taral
authors.initials: T
authors.lastname: Patel
authors.forename: Jonathan
authors.initials: J
authors.lastname: Polikoff
authors.forename: Mark
authors.initials: M
authors.lastname: Rubin
authors.forename: Leonard
authors.initials: L
authors.lastname: White
authors.forename: James Chih-Hsin
authors.initials: JC
authors.lastname: Yang
authors.forename: Chris
authors.initials: C
authors.lastname: Bowden
authors.forename: Vincent
authors.initials: V
authors.lastname: Miller
mesh_terms: D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D061067:Antibodies, Monoclonal, Humanized / Q000008:administration & dosage* / Q000009:adverse effects; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000627:therapeutic use*; D000068258:Bevacizumab; D002289:Carcinoma, Non-Small-Cell Lung / Q000188:drug therapy* / Q000401:mortality; D018572:Disease-Free Survival; D004311:Double-Blind Method; D000069347:Erlotinib Hydrochloride; D005260:Female; D006801:Humans; D053208:Kaplan-Meier Estimate; D008175:Lung Neoplasms / Q000188:drug therapy* / Q000401:mortality; D060046:Maintenance Chemotherapy / Q000379:methods*; D008297:Male; D008875:Middle Aged; D016016:Proportional Hazards Models; D011799:Quinazolines / Q000008:administration & dosage* / Q000009:adverse effects; D016896:Treatment Outcome
chemical_list: D061067:Antibodies, Monoclonal, Humanized; D011799:Quinazolines; D000068258:Bevacizumab; D000069347:Erlotinib Hydrochloride